以曲妥珠单抗 (trastuzumab)为代表的靶向治疗极大改善了HER2阳性乳腺癌、胃/食管癌患者的预后。但曲妥珠单抗的使用存在复发转移、肿瘤耐药及心脏毒性等显著的问题。本项目选取超小粒径的仿生黑色素(Melanin)纳米粒子对Trastuzumab修饰，以独创的分子量可控、pH敏感的聚乳酸为链，构建生物学可控、融合单抗和纳米粒子双重优势的多模态Her-MNP纳米平台，并通过偶联不同的金属离子实现PET/MRI/PAI多模型分子显像。Her-MNP能“欺骗”肿瘤细胞表面的P-糖蛋白将化疗药物带入胞内，并根据肿瘤微环境的变化缓释单抗以提高生物的利用度及降低其固有心脏毒性。本项目还将借助于分子影像技术，为乳腺癌治疗过程中耐药性和/或复发转移提前预警，并为HER2生物学行为密切相关的信号转导通路的提供可视化方法。Her-MNP的研究有望奠定基于单抗-纳米平台用于肿瘤分子靶向诊疗的理论基础。

Trastuzumab (Herceptin®) is an effective targeted therapy for HER2 positive metastatic breast cancer, Gastric and esophageal cancer. However, the critical problem of tumor recurrence and metastasis, therapy resistance and cardiac toxicity significantly remains to be a tough challenge. We using ultra small, bionic melanin nanoparticle for Trastuzumab modification in this project. The molecular defined and pH sensitive poly lactic acid will be designed as a ligand to connect between antibody and MNP. Bio-controllable Her-MNP nano platform will be constructed and evaluated for tumor multi-modality (PET/MRI/PAI) molecular imaging by coordinating with different metals. Her-MNP may "cheat" the P-glycoprotein which located on the surface the tumor, and accordance with the changes in the tumor micro-environment to improve the bio-availability of the drug and reduce its inherent cardiac toxicity. By advanced molecular imaging techniques, Her-MNP can monitor the expression of receptor in the progress of tumor in organ. It may give more visualized information which related to the HER2 pathway. Her-MNP is expected to lay a fundamental theoretical basis for tumor targeted molecular imaging based on monoclonal antibody and nano platform.